The Basics
What is Tenofovir?
Used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. Generally recommended for use with other antiretrovirals.
Brand names for Tenofovir
Atripla
How Tenofovir is classified
Anti-Infective Agents, Anti-HIV Agents, Antiviral Agents, Anti-Retroviral Agents, Reverse Transcriptase Inhibitors
Tenofovir During Pregnancy
Tenofovir pregnancy category
Category DNote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.
What we know about taking Tenofovir while pregnant
Antiretroviral Pregnancy Registry To monitor fetal outcomes of pregnant women, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients who become pregnant by calling (800) 258-4263. Efavirenz: As of July 2 , the Antiretroviral Pregnancy Registry has received prospective reports of 792 pregnancies exposed to efavirenz-containing regimens, nearly all of which were first-trimester exposures (718 pregnancies). Birth defects occurred in 17 of 604 live births (first-trimester exposure) and 2 of 69 live births (second/third-trimester exposure). One of these prospectively reported defects with first-trimester exposure was a neural tube defect. A single case of anophthalmia with first-trimester exposure to efavirenz has also been prospectively reported; however, this case included severe oblique facial clefts and amniotic banding, a known association with anophthalmia. There have been six retrospective reports of findings consistent with neural tube defects, including meningomyelocele. All mothers were exposed to efavirenz-containing regimens in the first trimester. Although a causal relationship of these events to the use of efavirenz has not been established, similar defects have been observed in preclinical studies of efavirenz. Animal Data Effects of efavirenz on embryo-fetal development have been studied in three nonclinical species (cynomolgus monkeys, rats, and rabbits). In monkeys, efavirenz 60 mg/kg/day was administered to pregnant females throughout pregnancy (gestation Days 20 through 150). The maternal systemic drug exposures (AUC) were 1.3 times the exposure in humans at the recommended clinical dose (600 mg/day), with fetal umbilical venous drug concentrations approximately 0.7 times the maternal values. Three fetuses of 20 fetuses/infants had one or more malformations; there were no malformed fetuses or infants from placebo-treated mothers. The malformations that occurred in these three monkey fetuses included anencephaly and unilateral anophthalmia in one fetus, microphthalmia in a second, and cleft palate in the third. There was no NOAEL (no observable adverse effect level) established for this study because only one dosage was evaluated. In rats, efavirenz was administered either during organogenesis (gestation Days 7 to 18) or from gestation Day 7 through lactation Day 21 at 50, 100, or 200 mg/kg/day. Administration of 200 mg/kg/day in rats was associated with an increase in the incidence of early resorptions, and doses 100 mg/kg/day and greater were associated with early neonatal mortality. The AUC at the NOAEL (50 mg/kg/day) in this rat study was 0.1 times that in humans at the recommended clinical dose. Drug concentrations in the milk on lactation Day 10 were approximately 8 times higher than those in maternal plasma. In pregnant rabbits, efavirenz was neither embryo lethal nor teratogenic when administered at doses of 25, 50, and 75 mg/kg/day over the period of organogenesis (gestation Days 6 through 18). The AUC at the NOAEL (75 mg/kg/day) in rabbits was 0.4 times that in humans at the recommended clinical dose.
Taking Tenofovir While Breastfeeding
What are recommendations for lactation if you're taking Tenofovir?
Published experience with tenofovir during breastfeeding in HIV-positive mothers and HIV-negative mothers treated for HIV prophylaxis or hepatitis B infection indicates that the exposure of the infant to the drug is trivial. A few infants have been breastfed during maternal tenofovir therapy and no adverse effects have been seen up to 2 years of age. Expert reviews of available data concluded that there is currently no justification for contraindicating the use of tenofovir for hepatitis B during breastfeeding.[1][2] Professional organization guidelines generally allow breastfeeding during tenofovir therapy, although one guideline cautions against it because of a lack of long-term safety data.[3][4][5] The lack of long-term safety data with long-term, low-level infant exposure should be discussed with the mother.[3] No differences exist in infection rates between breastfed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth. Mothers with hepatitis B are encouraged to breastfeed their infants after their infants receive these preventative measures.[6][7] Maternal use of prophylactic vaginal tenofovir (investigational in the U.S.) does not appear to present a great risk to the breastfed infant.[8] In the United States and other developed countries, HIV-infected mothers should generally not breastfeed their infants. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, World Health Organization guidelines recommend that all women with an HIV infection who are pregnant or breastfeeding should be maintained on antiretroviral therapy for at least the duration of risk for mother-to-child transmission. Mothers should exclusively breastfeed their infants for the first 6 months of life; breastfeeding with complementary feeding should continue through at least 12 months of life up to 24 months of life.[9] The first choice regimen for nursing mothers is tenofovir, efavirenz and either lamivudine or emtricitabine. If these drugs are unavailable, alternative regimens include: 1) zidovudine,
Maternal / infant drug levels
Published experience with tenofovir during breastfeeding in HIV-positive mothers and HIV-negative mothers treated for HIV prophylaxis or hepatitis B infection indicates that the exposure of the infant to the drug is trivial. A few infants have been breastfed during maternal tenofovir therapy and no adverse effects have been seen up to 2 years of age. Expert reviews of available data concluded that there is currently no justification for contraindicating the use of tenofovir for hepatitis B during breastfeeding.[1][2] Professional organization guidelines generally allow breastfeeding during tenofovir therapy, although one guideline cautions against it because of a lack of long-term safety data.[3][4][5] The lack of long-term safety data with long-term, low-level infant exposure should be discussed with the mother.[3] No differences exist in infection rates between breastfed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth. Mothers with hepatitis B are encouraged to breastfeed their infants after their infants receive these preventative measures.[6][7] Maternal use of prophylactic vaginal tenofovir (investigational in the U.S.) does not appear to present a great risk to the breastfed infant.[8] In the United States and other developed countries, HIV-infected mothers should generally not breastfeed their infants. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, World Health Organization guidelines recommend that all women with an HIV infection who are pregnant or breastfeeding should be maintained on antiretroviral therapy for at least the duration of risk for mother-to-child transmission. Mothers should exclusively breastfeed their infants for the first 6 months of life; breastfeeding with complementary feeding should continue through at least 12 months of life up to 24 months of life.[9] The first choice regimen for nursing mothers is tenofovir, efavirenz and either lamivudine or emtricitabine. If these drugs are unavailable, alternative regimens include: 1) zidovudine, lamivudine and efavirenz; 2) zidovudine, lamivudine and nevirapine; or 3) tenofovir, nevirapine and either lamivudine or emtricitabine. Exclusively breastfed infants should also receive 6 weeks of prophylaxis with nevirapine.[10][11] Use of tenofovir as an agent for pre-exposure prophylaxis (PrEP) in HIV-uninfected nursing mothers appears to pose little risk to their breastfed infants and might prevent vertical HIV transmission by preventing maternal infection.[12] Treatment of mothers of HIV+ mothers with efavirenz as part of Option B+ therapy does not appear to affect growth of their HIV-negative breastfed infants.
Possible effects of Tenofovir on milk supply
Relevant published information was not found as of the revision date.
Possible alternatives to Tenofovir
(Hepatitis B) Interferon Alfa, Lamivudine.
List of References
Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/
1. Ehrhardt S, Xie C, Guo N, Nelson K, Thio CL. Breastfeeding while taking lamivudine or tenofovir disoproxil fumarate: a review of the evidence. Clin Infect Dis. 2015;60:275-8. PMID: 25313254
2. Mofenson LM , Baggaley RC, Mameletzis I. Tenofovir disoproxil fumarate safety for women and their infants during pregnancy and breastfeeding: Systematic review. AIDS. 2017;31:213-23. PMID: 27831952
3. Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016;63:261-83. PMID: 26566064
4. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370-98. PMID: 28427875
5. Sarin SK, Kumar M, Lau GK et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: A 2015 update. Hepatol Int. 2016;10:1-98. PMID: 26563120
6. Visvanathan K, Dusheiko G, Giles M et al. Managing HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up: Position paper produced by Australian, UK and New Zealand key opinion leaders. Gut. 2016;65:340-50. PMID: 26475631
7. Dionne-Odom J, Tita AT, Silverman NS. #38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol. 2016;214:6-14. PMID: 26454123
8. Noguchi LM, Montgomery ET, Biggio JR et al. Detectable tenofovir levels in breastfeeding infants of mothers exposed to topical tenofovir. Antimicrob Agents Chemother. 2016;60:5616-9. PMID: 27401570
9. Anon. Guideline: Updates on HIV and infant feeding: The duration of breastfeeding, and support from health services to improve feeding practices among mothers living with HIV. Geneva: World Health Organization. 2016. PMID: 27583316
10. World Health Organization. HIV and infant feeding: update. 2007. http://whqlibdoc.who.int/publications/2007/9789241595964_eng.pdf
11. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Geneva: World Health Organization. 2013. http://www.who.int/hiv/pub/guidelines/arv2013/en/
12. Mugwanya KK , John-Stewart G, Baeten J. Safety of oral tenofovir disoproxil fumarate-based HIV pre-exposure prophylaxis use in lactating HIV-uninfected women. Expert Opin Drug Saf. 2017;1-5. PMID: 28571500
13. Benaboud S, Pruvost A, Coffie PA et al. Concentrations of tenofovir and emtricitabine in breast milk of HIV-1-infected women in Abidjan, Cote d’Ivoire, in the ANRS 12109 TEMAA Study, step 2. Antimicrob Agents Chemother. 2011;55:1315-7. PMID: 21173182
14. Mirochnick M, Taha T, Kreitchmann R et al. Pharmacokinetics and safety of tenofovir in HIV-infected women during labor and their Infants during the first week of life. J Acquir Immune Defic Syndr. 2014;65:33-4. PMID: 23979002
15. Palombi L, Pirillo MF, Marchei E et al. Concentrations of tenofovir, lamivudine and efavirenz in mothers and children enrolled under the Option B-Plus approach in Malawi. J Antimicrob Chemother. 2016;71:1027-30. PMID: 26679247
16. Mugwanya KK, Hendrix CW, Mugo NR et al. Pre-exposure prophylaxis use by breastfeeding HIV-uninfected women: A prospective short-term study of antiretroviral excretion in breast milk and infant absorption. PLoS Med. 2016;13:e1002132. PMID: 27676257
17. Waitt C, Diliiy Penchala S, Olagunju A et al. Development, validation and clinical application of a method for the simultaneous quantification of lamivudine, emtricitabine and tenofovir in dried blood and dried breast milk spots using LC-MS/MS. J Chromatogr B Anal Technol Biomed Life Sci. 2017;1060:300-37. PMID: 28651173
18. Waitt C, Olagunju A, Nakalema S et al. Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother-infant pairs. J Antimicrob Chemother. 2018;73:1013-9. PMID: 29309634
19. Erturk US, Mete B, Ozaras R et al. The determination of tenofovir level in breast milk of nursing mothers under tenofovir therapy. Hepatology. 2018;68 (Suppl 1):256A-7A. Abstract.
20. Gouraud A, Millaret A, Bernard N, Bruel M, Paret N, Descotes J et al. Tenofovir exposure through breast feeding: Serum concentrations in neonates and clinical follow-up. Fundam Clin Pharmacol. 2012;26 (Suppl 1):9. Abstract. DOI: doi:10.1111/j.1472-8206.2012.01032.x
21. Gibb DM, Kizito H, Russell EC et al. Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial. PLoS Med. 2012;9:e1001217. PMID: 22615543
22. Pan CQ, Mi LJ, Bunchorntavakul C et al. Tenofovir disoproxil fumarate for prevention of vertical transmission of hepatitis B virus infection by highly viremic pregnant women: A case series. Dig Dis Sci. 57:2423-9. PMID: 22543886
23. Ganne-Carrie N, Causse X, Zarski JP et al. Efficacy and safety results of tenofovir DF (TDF) treatment from the first trimester in HBV pregnant women in real-life clinical practice. Hepatology. 2013;58 (Suppl 1):664A-5A. Abstract. DOI: doi:10.1002/hep.26855
24. Floridia M, Liotta G, Andreotti M et al. Levels of bone markers in a population of infants exposed in utero and during breastfeeding to tenofovir within an Option B+ programme in Malawi. J Antimicrob Chemother. 2016;71:3206-11. PMID: 27494909
25. Marcellin P, Zoulim F, Hezode C et al. Effectiveness and safety of tenofovir disoproxil fumarate in chronic hepatitis B: A 3-year, prospective, real-world study in France. Dig Dis Sci. 2016;61:3072-83. PMID: 26821154
26. Kapito-Tembo AP, Wesevich A, Bauleni A et al. Growth in infants exposed to EFV and TDF through breastmilk: Malawi PMTCT option B+. Top Antiviral Med. 2017;25:333s-4s. Abstract.
27. Wang M, Bian Q, Zhu Y, Pang Q, Chang L, Li R et al. Real-world study of tenofovir disoproxil fumarate to prevent hepatitis B transmission in mothers with high viral load. Aliment Pharmacol Ther. 2018;49::211-7. PMID: 30506691
Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.
